Cardiac illness presently the first death factor in the industrial world, well before cancer. A considerable number of adults die prematurely of an unreversible heart failure, whereas their other vital functions are perfectly sane.
The causes of this plague are numerous and still obscure for the most part. Hence preventive measures cannot have a really significant effect.
Surgical techniques of bridging obstructing lesions of coronaty vessels are very efficient, since more than 400,000 sick persons are operated in the world each year. Unhappily, this surgery remains often palliative or insufficient.
Only for the United States, more than 8000 sick persons die each year during or immediately after a surgical operation on the heart; more than 100,000 sick persons, less than 65 years old, die each year of the immediate consequences of a myocardium infarct; finally, more than 50,000 sick persons, less than 65 years old die from a final invalidating cardiac insufficiency consecutive to one or several repeated infarcts.
Cardiac transplantation, i.e. the grafting on a sick receiving person of a natural heart taken from a donor, has today a renewed interest in view of the efficiency of a new specific pharmacological agent reducing the immunologic rejections pheomena. Unhappily, the shortage of available donors makes it impossible to meet the needs.
The number of applicants waiting for a cardiac transplantation increases. Many of them die prematuraly before an acceptable graft be available.
The graft of an articifial heart, mechanical alternative to the cardiac transplantation, seems accordingly to be the only solution of the future.
In order to become operative, this solution must however be of clinically acceptable form and comply with the standards of performance, confort, security and liability required by the international medical community.
More than 25 years of intensive searches and several thousands experimentations on animals in laboratories allow to consider to-day this alternative as achievable.
The history of these searches on artificial heart, the present state of the art and the prospects for the end of the nineteen eighties have been recently set forth by John T. WATSON, in charge of this field for the U.S. Federal Government, in:
"Past, Present, and Future of Mechanical Circulatory Support" J. T. WATSON, Chief, Devices and Technology Branch Division--of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute PA0 Third International Symposium on heart substitution. ROMA, ITALIE, MAY 17, 1982. PA0 1. THE ARTIFICIAL HEART, William S. PIERCE Archives of Surgery, Vol. 112, December, 1977, page 1430-1438 PA0 2. CRITERIA FOR HUMAN TOTAL ARTIFICIAL HEART IMPLANTATION BASED ON STEADY STATE ANIMAL DATA. Robert K. JARVIK Trans. American Society For Artificial Internal Organs. Vol. XXIII 1977 page 533-542 PA0 3. APPROACHES TO THE ARTIFICIAL HEART, WILLIAM PIERCE Surgery, 90, 137.1981 PA0 4. THE TOTAL ARTIFICAL HEART. Robert K. JARVIK Scientificic American, 244. 74. 1981 PA0 5. THE ARTIFICIAL HEART William S. PIERCE Thoracic and cardio-vascular Surgery Editor. William W. L. GLENN, M.D. 1983. APPLETON CENTURY CROFTS PA0 6. PRISE EN CHARGE DEFINITIVE DE LA FONCTION CARDIAQUE PAR LE COEUR ARTIFICIEL. Didier LAPEYRE. Compte-rendus des seances de la Societede Biologie du College de France. Tome 175. N.degree.5. 1981. p.559 PA0 7. JOURNAL OF THE INTERNATIONAL SOCIETY FOR ARTIFICIAL ORGANS. Feb. 1983. CLEVELAND Vol. 7 Number 1, Raven Press. PA0 8. TOTAL ARTIFICIAL HEART IN TWO-STAGED CARDIAC TRANSPLANTATION Denton A. COOLEY et Al. Cardio-vascular diseases Bulletin of the Texas Heart Institute Volume 8, Number 3, September 1981 PA0 9. SADE, R. M., CASTANEDA A. R. THE DISPENSIBLE RIGHT VENTRICLE Surgery 77: 624-631. 1975 PA0 10. TOTAL SUPPORT OF THE CIRCULATION OF A PATIENT WITH POST-CARDIOTOMY STONE-HEART SYNDROME by a PARTIAL ARTIFICIAL HEART (ALVAD) FOR 5 DAYS . . . Lancet 1: 1125, 1978. Denton A. COOLEY et AL. PA0 THE IMPLANTATION OF THE TOTAL ARTIFICIAL HEART FOR THE TREATMENT OF END STAGE CARDIOMYOPATHY. W. C. De Vries and Al. Salt-Lake-City, Utah. PA0 62nd Annual Meeting of the American Association for Thoracic Surgery. ATLANTA, Ga. Apr. 27, 1983.
NATIONAL INSTITUTES OF HEALTH, Bethesda, Md., U.S.A.
Several recent papers summarize more accurately the present situation of the practical achivements and the critical problems encountered. They are:
The two further following papers are of importance for the understanding of the present invention:
On Dec. 2, 1982 the first human application of definitive substitution to a failing natural heart of a total cardiac prothesis has been made by the surgical team of SALT. LAKE CITY (DE VRIES, JARVIK, OLSEN et Al.). This first test has been widely commented throughout the world. The first human being with an artificial heart lived 112 days with a total prothesis and an extra-body pneumatic control, conventional device commonly used on animals since more than 15 years in all the laboratories involved in this research.
In spite of a few incidents, the first utilisation on human being has proved definitely that it was possible to take over the human circulatory function by mechanical means and it has been established that the cause of the patient death was not directly linked to the cardiac prothesis. See on this subject:
The acquired knowledge in the state of the art, recalled in the above-mentioned papers, may be summarized in three essential observations:
(1) Since 25 years, all the experimenters which could obtain long survivals (several months) on animal, have exclusively used a pair of membrane blood pumps replacing the two ventricles of the natural heart, and an extra-body pneumatic activation. Very numerous solutions have been proposed to integrate the actuation system in the two blood pumps. However, all the devices attempting to integrate the mechanical actuation system to the blood pumps were abandonned since the weight, the excessive volume and the heat evolution are incompatible with the anatomical, physiological and biological requirements.
It has thus been necessary to uncouple the blood pumps located in the pericardium cavity from their mechanical actuation device.
However, several systems are presently developed for replacing the heavy and bulky external pneumatic console with an electro-hydraulic, electro-pneumatic of electromechanical miniaturized converter, adapted to an implantation near the blood pumps, either in the thorax or in the abdomen.
Technically more realistic solutions are those of electro-hydraulic type (see U.S. Pat. Nos. 4,173,796 and 4,369,530) or of the electro-penumatic type.
Up to day, only one attempt of integration of the actuation means has been successful. It is that (see reference 5 above), developed by ROSENBERG and PIERCE, making use of an electromechanical converter with a pushing plate compressing blood bags of hemocompatible elastomers. A veal survived 225 days in good conditions. This is a world record of historical importance, since the animal has normally lived with a completely implanted prothesis fed externally by an electric power source. The required power was only 10 watts, whereas the weight of the animal was more than 180 kgs, i.e. twice that of a standard human dault.
However, the volume of this prothesis (900 cc) and its weight (1.1. kg) are redhibitory for human application and the miniaturizing possibilities of such an apparatus seem very limited.
The installation of machined mechanical parts in the cardiac prothesis itself, according to a configuration conforming with the shape, the volume and the weight of natural heart, appears in fact, from a technological point of view, as an insurmountable challenge.
Of course, the blood volume displaced during each cycle might be reduced to 40 or 50 cc, which would result in an important room saving. However, this reduction should obligatorily result in an increase of the operational basic frequency for maintaining an acceptable heart delivery rate. The obtained compensation would thus heavily reduce the life-time of the components.
(2) In view of the considerable difficulties encountered by the research teams at the beginning of the nineteen seventies, in order to maintain animals alive for an extended period, even when the actuation is effectued through an extra-body pneumatic console, the U.S. National Institute of Health has decided, in 1975, to devote more efforts to another alternative search way, i.e. the left ventricle assistance.
In this alternative, the ill natural heart is kept in place. An accessory artificial ventricle is parallelly branched on the circulation system and by-passes the ill left ventricle. The left ventricle is in fact the true "heart". It assumes the perfusion of all the organs under a working pressure of ten times that of the pulmonary circulation (right ventricle).
It is responsible for almost the totality of the cardiac pathology.
Conversely, it must be recalled that the right ventricle only perfuses the pulmonar tissue and that, in normal conditions, its motive function on the circulating blood is very low.
The concept of parallel operation of the ill left ventricle and of an artificial assisting ventricle is hence th the more attractive as it maintains the natural heart in place, which is a much less radical process than a complete replacement. To the mere extent of psychological and emotional aspect, the left ventricle assistance seems thus a priori as a more "practical" solution.
In a known manner the left ventricle prothesis is placed either in the thorax or under the diaphragm, in the abdomen cavity.
It may comprise an integrated system of mechanical actuation, since the bulk limitations are much less severe in the pericardium cavity.
For yield reasons, the preferred devices are mostly of the type with a pushing plate . Five apparatuses of this type has been developed since 1977.
These apparatuses are described by FRANK D. ALTIERI in a recent paper (see reference 7 above, pages 5 to 20): "Status of Implantable Energy System to Actuate and Control Ventricular Assist Devices".
Two integrated systems which can be fed from an implanted isotopic power source or from a thermal battery are also in development: University of Washington (Modified Stirling Engine) and AEROJET system (Stirling Cycle Thermo-Compressor).
Where using an electric power source, the power is transmitted through the skin, either percutaneously by use of specific materials well tolerated by the skin (carbon derivatives, polycarbonate, polytetrafluoroethylene, etc . . . ) or transcutaneously, by high frequency magnetic induction on a primary winding implanted under the skin.
The accumulated experience, as well in laboratory as in human clinic, shows that the concept of left ventricle assistance suffers, in fact, from two major disadvantages which oblige to very seriously reconsider its potential utility in human clinic.
Besides, from a technical point of view, some critical points have not yet found an acceptable solution:
Only by itself, an accessory left pump branched in parallel on the failing natural left ventricle, cannot assume the totality of the cardiac function.
More than 150 attempts have been made on human being without conclusive results. In a few cases, of short duration, the left ventricle by-pass has allowed a few sick persons having an acute insufficiency of left ventricle to pass a difficult cape, immediately following a surgical operation of the heart.
These cases are unhappily very scarce. Although the U.S. National Institute of Health has autorized application to human being, in various cardiology centers, since 1979, the method was not conclusive for the users. Some of its promoters, such as DENTON A. COOLEY, have even given up.
For sick persons with an invalidating left ventricle chronic insufficiency (theoretically the best indication for ventricle assistance), the cardiologists and heart surgeons are higly reluctant to use a heavy method which may hasten the fatal termination and which, in every case, is conditioned by the aleatory possible failure of the right ventricle function.
Moreover, it is considered that the relief of the sick left ventricle by the auxiliary artificial ventricle would favor the progressive decrease of the right ventricle performances. (see: EFFETCS OF LEFT HEART BY-PASS ON RIGHT VENTRICULAR FUNCTIONS, A. T. MIYAMOTO et Al. Vol. XXVIII TRANS AM. SOC. ARTIF. INTERN ORGANS 1983, page 543).
Finally, two critical technical points yet remain unsolved:
1. The placing of a membrane either in the tip of the sick left ventricle or upstream thereto in the left auricle, results in phenomena of mechanical impediment to the feeding of the accessory ventricle (plicatures, bendings, pressure drops, resulting from an insufficient section, coagulation . . . ).
2. The rate of delivery of the auxiliary left ventricle must be controlled by the feeding pressure of the natural left ventricle, itself function of the delivery of the right ventricle. In the case where the venous return delivery decreases, for example at rest, the blood by pass rate through the auxiliary ventricle may be very low, thus producing in the feeding duct of the auxiliary ventricle the formation of a cellular proliferation ("pannus") which tends to progressively obstruct it, since this phenomenon, once begun, self-develops for obvious hydraulic reasons.
To resume, the experience of these twenty-five last years, as well in the field of total heart replacement as in that of left ventricular assistance, gives the following informations, well-known in the art:
(1) It is to-day technically impossible to connect, in the pericardium cavity of a human being, in lieu of the failing natural heart, a total cardiac prothesis and its mechanical actuation system, in view of the fact that the natural heart of a man has, as an average, a weight from 300 to 350 g and that of a woman 250 to 300 g, and, when the heart is full with blood (diastole), its volume does not exceed 550 cc.
Of course, numerous cardiac sick persons suffer from a substantial increase of the heart volume ("cardiomegaly").
Unhappily, the very large majority of applicants for a total cardiac replacement by artificial heart pertain to the category of ischiema cardiomyopathes with coronaty lesions. These sick persons do not suffer from a significant increase of the heart volume.
A total cardiac prothesis must not have a weight and a volume substantially greater than the weight and the volume of the natural heart. Bulk linitations are not only of physical order (available volume); they have, in fact, operational critical effects, as shown hereinafter. It is thus necessary to anatomically uncouple the intra-pericardial blood pumps from the mechanical devices actuating said pumps.
(2) Several thousands of experimentations on animal, and a few ones on human being, have shown that it was possible to place, externally to the pericardium cavity, either in the thorax or in the abdomen cavity, or in retro-peritoneal position a pump and its actuation means. Such spaces are considered as "physiologically neutral" and they can easily receive mechanical systems of a volume larger than 900 cc, for a weight which may reach, without inconvenience, 1000 to 12000 grams.
(3) The U.S. Pat. Nos. 4,173,796, 4,222,127 and 4,369,530, recall, in a general and non exhaustive manner, the main technical objects to achive when making a standardized total cardiac prothesis able to efficiently replace a failing human natural heart, in an acceptable technical form.
It will be observed that some of these objects are not yet achieved and constitute critical points well known in the art.
These critical points must however be classified according to a fundamental priority order, since the solution of some of them depends on solutions which can be found for others. This hierarchy of priorities must be expressed clearly.
First of all, anatomic requirements must be complied with, since they have a critical incidence on the prothesis function. A cardiac prothesis must obviously reproduce the pumping capacity, if not of an athlete natural jeart, at least of a heart graft taken from a donor. Th functional capacities must allow a sick person with a transplanted heart to move, to make current exercises such as walk, or even swimming. Studies on sick persons having undergone a cardiac transplantation have shown that the capacities ("pumping capacities") of a prothesis should range between the limit values of 3 and 10 1. per minute.
Although the delivery rate varies in accordance with the metabolic demands within the above-mentioned limits, it should be observed that the average delivery rate for a standard adult is about 4 liters per minute during more than 95% of the time. Finally, the frequency varies only to a small extent and remains close to 70 cycles per minute, with a distribution in the cycle of the order of 35% for the systole and 65% for the filling time, the frequency variations being essentially the result of a variation in the filling time whereas the systole time remains substantially constant (with 5% of variation).
Another fundamental point to be recalled, closely related to the first one, is an elementary physiological notion, universal by admitted to-day, but which was yet controversial during the last ten years. The heart is a response-organ, whose funtional capacities must assume variations in the feeding rate, which variations are themselves related to variations of the metabolic activity of the organism. In other terms, the cardiac pump is the slave and the organism is the master. This fundamental principle makes necessary a control of the delivery rate based on the variations of the return flow rate, the pilot signal being the return blood pressure, since an increase of metabolic demands of the organism results in a decrease in the resistance of the circuit, producing an increase of the return flow rate. The natural cardiac pump reacts with a very high sensitivity, by variations in the frequency of the pulsed volume and in the contraction force, to variations of the feeding pressure and to the variations of the output resistance. This sensitivity has been measured. It is about of one liter per minute and per mercury millimeter of pressure. Thus, practically, an artificial heart must react to an increase of the feeding pressure of the right heart of about 10 millimeters of mercury by a variation of the delivery rate from 3 to 10 liters per minute within a relatively short response time, not exceeding a few seconds.
A third fundamental point is still of physiological order. The cardiac pump is fed through two veins of large diameter, i.e. vena cava superior and vena cava inferior, opening in a feeding reservoir formed by the right auricle. Similarly, the left ventricle is fed throught four pulmonary veins, i.e.; the right superior and inferior pulmonary veins and the left superior pulmonary veins, opening in the feeding reservoir formed by the left auricle. These veins and feeding reservoirs are very flexible and hence can be easily compressed when the bulk of the cardiac prothesis is excessive. These veins or ducts without radial rigidity are hence radially collapsable, which forbids any aspiration or active depression to; facilitate the filling. These particular filling structures are thus an essential critical point which is the more important as the ratio pressure/volume (compliance) of the upstream venous network is very low. A small increase in the resistances to filling of the cardiac pump thus results in a pressure increase in the network, which produces a very substantial increase in the volume of the venous circuit. A substantial part of the circulating volume may thus be kept in reserve or retained in the venous circuit, thus decreasing to the same extent the input flow to the blood pump.
The problem of adapting the shape, the volume and the weight of the cardiac prothesis to the free space made available in the pericardium cavity by ablation of the sick natural heart is not only a problem of physics, geometry and volume. The limitations as to the shape, the volume and the weight have, in addition, for the above-explained reasons, a direct determinent effect on the return flow rate, and hence on the functional characteristics of the cardiac pump.
By successive approaches and multiple slight adaptations, it has been possible, after several thousands of experimentations on animal, to solve in an acceptable manner this problem of adaptation in shape, volume and xeight on animal, which explains the extended survival today currently obtained in laboratory.
However, the anatomical limitations of human being are radically different from those of the animal and the results obtained by experimentation on animals cannot, in this field, be transposed to the human being. It is clear, in pratice for the cardiac surgeon, that the geometry of the cardiac prothesis must before all coincide into the configuration of the space left available by the ablation of the sick natural heart. On the contrary it is not acceptable that the thorax cavity of the sick person will have to conform to the geometry of the prothesis. Now, the applicants for receiving the cardiac prothesis are selected from those who have a pericardium cavity as large as possible in ordre to be able to house a bulky prothesis.
It must be further observed that this bulky prothesis cannot be directly coupled in the pericardium with a mechanical actuation system. As a matter of fact, such mechanical actuation systems will still increase the volume of the prothesis. It is hence necessary to provide the prothesis, but outside the pericardium, with electropneumatic of electro-hydraulic converters. But then the total yield of such prothesis is relatively low and a source of relatively high power (about 10 to 15 Watts) must be necessary.
In the present state of the art, in the field of the most performing electric generators, a 10 Watts power cannot be provided but by a battery of a weight higher than 1 kg, in order to obtain a complete autonomy of more than 3 hours with a portable battery. This results in constraints which are, for the patient, a factor of uncomfort. Moreover, the relatively low yield of the electro-pneumatic and electro-hydraulic converters results in a heat evolution liable to generate hot points in the converter.
In addition to the anatomical and psychological limitations, mentioned above, while taking into account the geometry, the weight and the volume of the artificial blood pump which must replace the failing natural heart, other standards must obligatorily be complied with in order that the artificial heart become effectively acceptable in human clinic. These standards are much, better explained in the state of the art than the anatomical and psychological limitations which, nevertheless, are prioritary.
These standards are of three orders, i.e.: biological, technological and economical (the cost of a prothesis must be as low as possible).
The biological standards concern the use of specific materials for the parts of the blood pumps which are in contact with the blood stream. These materials must be neutral vis-a-vis to the natural biological phenomena which condition the blood coagulation, when blood is in contact with an extraneous surface; These materials must, in addition, be non-toxic and must not generate local inflammatory reactions. Presently, a certain number of flexible plastic materials are used successfully for making membrane pumps.